The marketed drug, a meglumine salt, has completed an 18 month placebo controlled phase II/III clinical trial,[5][6] and an 18 month extension study which provides evidence that tafamidis slows progression of Familial amyloid polyneuropathy.[7] Tafamidis (20 mg once daily) is used in adult patients with an early stage (stage 1) of familial amyloidotic polyneuropathy.[8][9]

Tafamidis was discovered in the Jeffery W. Kelly Laboratory at The Scripps Research Institute[10] using a structure-based drug design strategy[11] and was developed at FoldRx pharmaceuticals, a biotechnology company led by Richard Labaudiniere that was acquired by Pfizer in 2010.

Tafamidis functions by kinetic stabilization of the correctly folded tetrameric form of the transthyretin (TTR) protein.[12] In patients with FAP, this protein dissociates in a process that is rate limiting for aggregation including amyloid fibril formation, causing failure of the autonomic nervous system and/or the peripheral nervous system (neurodegeneration) initially and later failure of the heart. Kinetic Stabilization of tetrameric transthyretin in familial amyloid polyneuropathy patients provides the first pharmacologic evidence that the process of amyloid fibril formation causes this disease, as treatment with tafamidis dramatically slows the process of amyloid fibril formation and the degeneration of post-mitotic tissue.

The process of wild type transthyretin amyloidogenesis also appears to cause senile systemic amyloidosis leading to cardiomyopathy as the prominent phenotype [13] Some mutants of transthyretin, including V122I primarily found in individuals of African descent, are destabilizing enabling heterotetramer dissociation, monomer misfolding, and subsequent misassembly of transthyretin into a variety of aggregate structures [14] including amyloid fibrils[15] leading to familial amyloid cardiomyopathy.[16] While there is clinical evidence from a small number of patients that tafamidis slows the progression of the transthyretin cardiomyopathies, this has yet to be demonstrated in a placebo controlled clinical trial.

In June 2012, the FDA Peripheral and Central Nervous System Drugs Advisory Committee voted 4-13 to reject drug the drug, stating there was little data supporting drug efficacy. The drug did not prevent neurologic deterioration or improve neurologic functional scores (both primary outcomes). However, the committee voted 13-4 that the existing data supported a secondary endpoint of reducing the number of patients who chose liver transplantation. The FDA requested a second clinical trial, which is likely to be completed in early 2014.[17]